NEW DRUGS FOR OPPORTUNISTIC INFECTIOUS DISEASES

获得性免疫缺陷综合症（艾滋病）的特点是 在免疫系统中表现为严重的 机会性感染 这种感染的治疗往往是 由于各种原因，包括缺乏有效的 抗菌治疗 最常见的艾滋病相关真菌和细菌 机会性感染是隐球菌病，念珠菌病，组织胞浆菌病， 和分枝杆菌病。 历史上，大多数细菌感染和局部真菌感染 已经被临床上众多的 可用的抗生素。 然而，需要新的、更有效的和 毒性较小的抗生素用于治疗播散性真菌， 分枝杆菌感染是显而易见的， 目前可用药物的毒性和失败率。 的 过去，新抗生素的发现成功地依赖于 主要基于从天然来源中分离这些试剂。 的 这种方法相对于化学合成或修饰的主要优点 现有药物的最大优势是发现新的原型药物的可能性 化学结构完全不同，因此， 相似的毒性、交叉耐药性和作用机制。 虽然 微生物传统上是新的微生物的主要来源。 抗生素，最近已经表明，高等植物也可以作为 许多不同的和新颖的抗微生物剂的来源。 该项目的目标是发现新的原型抗生素 具有潜在的效用，特别是用于治疗艾滋病相关的 机会性播散性真菌病和分枝杆菌病。 这一目标将 通过抗真菌药物的初步体外评价完成， 高等植物提取物的抗分枝杆菌活性。 植物提取物 其显示良好的活性，将使用 生物测定指导方案。 这种方法确保了相对较少的 在分离非活性材料时将浪费时间和精力。 纯 具有显著最小抑菌浓度（MIC）的活性化合物 将在已建立的动物模型中评价体内疗效， 传播性真菌病和分支杆菌病，以确定其 潜在的临床应用。

Acquired Immunodeficiency Syndrome (AIDS) is characterized by a breakdown in the immune system which is manifested in the form of serious opportunistic infections. Treatment of such infections is often inadequate for a variety of reasons, including the lack of effective antimicrobial therapy. The most common AIDS-related fungal and bacterial opportunistic infections are cryptococcosis, candidiasis, histoplasmosis, and mycobacteriosis. Historically, most bacterial infections and localized fungal infections have been effectively treated with one of the numerous clinically available antibiotics. However, the need for new, more effective and less toxic antibiotics for the treatment of disseminated fungal and mycobacterial infections is obvious in light of the significant toxicities and failure rates of the currently available agents. The discovery of new antibiotics has in the past successfully relied primarily upon the isolation of such agents from natural sources. The major advantage of this approach over chemical synthesis or modification of existing agents is the likelihood of identifying new prototype drugs with quite different chemical structures, and hence, less likelihood of similar toxicities, cross-resistance, and mechanisms of action. Although microorganisms have traditionally served as the primary source of new antibiotics, it has recently been shown that higher plants also serve as sources for a number of diverse and novel antimicrobial agents. The objective of this project is to discover new prototype antibiotics with potential utility specifically for the treatment of AIDS-related opportunistic disseminated mycoses and mycobacteriosis. This goal will be accomplished by the initial in vitro evaluation of antifungal and antimycobacterial activity of extracts of higher plants. Plant extracts which show good activity will be fractionated and purified using a bioassay-directed scheme. This approach ensures that relatively little time and effort will be wasted in isolating inactive materials. Pure active compounds with significant minimum inhibitory concentrations (MIC) will be evaluated for in vivo efficacy in established animal models of disseminated mycosis and mycobacteriosis in order to determine their potential clinical utility.